title: Structures and reaction mechanisms of the two related enzymes, PurN and PurU.
abstract: The crystal structures of glycinamide ribonucleotide transformylases (PurNs) from Aquifex aeolicus (Aa), Geobacillus kaustophilus (Gk) and Symbiobacterium toebii (St), and of formyltetrahydrofolate hydrolase (PurU) from Thermus thermophilus (Tt) were determined. The monomer structures of the determined PurN and PurU were very similar to the known structure of PurN, but oligomeric states were different; AaPurN and StPurN formed dimers, GkPurN formed monomer and PurU formed tetramer in the crystals. PurU had a regulatory ACT domain in its N-terminal side. So far several structures of PurUs have been determined, yet, the mechanisms of the catalysis and the regulation of PurU have not been elucidated. We, therefore, modelled ligand-bound structures of PurN and PurU, and performed molecular dynamics simulations to elucidate the reaction mechanisms. The evolutionary relationship of the two enzymes is discussed based on the comparisons of the structures and the catalytic mechanisms.
authors.affiliation: Department of Engineering Science, Graduate School of Informatics and Engineering, The University of Electro-Communications, 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan; RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Sayo, Hyogo 679-5148, Japan; Structural Biology Group, SPring-8/JASRI, 1-1-1 Kouto, Sayo, Sayo, Hyogo 679-5198, Japan; Department of Life and Environmental Sciences, Faculty of Engineering, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan; and Department of Biological Sciences, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka 560-0043, Japan.
authors.forename: Gen-ichi
authors.initials: G
authors.lastname: Sampei
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kanagawa
authors.forename: Seiki
authors.initials: S
authors.lastname: Baba
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shimasaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Taka
authors.forename: Shohei
authors.initials: S
authors.lastname: Mitsui
authors.forename: Shinji
authors.initials: S
authors.lastname: Fujiwara
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yanagida
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kusano
authors.forename: Sakiko
authors.initials: S
authors.lastname: Suzuki
authors.forename: Kayoko
authors.initials: K
authors.lastname: Terao
authors.forename: Hiroya
authors.initials: H
authors.lastname: Kawai
authors.forename: Yoko
authors.initials: Y
authors.lastname: Fukai
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakagawa
authors.forename: Akio
authors.initials: A
authors.lastname: Ebihara
authors.forename: Seiki
authors.initials: S
authors.lastname: Kuramitsu
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Gota
authors.initials: G
authors.lastname: Kawai
mesh_terms: D039903:Actinobacteria / Q000201:enzymology; D000494:Allosteric Regulation; D029063:Aquifoliaceae / Q000201:enzymology; D055162:Biocatalysis; D056506:Geobacillus / Q000201:enzymology; D006867:Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D051026:Phosphoribosylglycinamide Formyltransferase / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D016963:Thermus thermophilus / Q000201:enzymology
chemical_list: D051026:Phosphoribosylglycinamide Formyltransferase; D006867:Hydrolases
keywords: X-ray crystallography; metabolic pathway; molecular evolution; purine synthesis; reaction mechanism